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Displaying record number 1619
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MAb ID |
m9 (scFv m9) |
HXB2 Location |
Env |
Env Epitope Map
|
Author Location |
gp120 |
Research Contact |
Zhang2004 |
Epitope |
|
Ab Type |
gp120 adjacent to CD4bs |
Neutralizing |
P |
Species
(Isotype)
|
human(IgG) |
Patient |
FDA2 |
Immunogen |
in vitro stimulation or selection |
Keywords |
antibody binding site, antibody generation, antibody interactions, assay or method development, autoantibody or autoimmunity, co-receptor, effector function, enhancing activity, escape, immunotherapy, neutralization, review, structure, subtype comparisons, variant cross-reactivity |
Notes
Showing 14 of
14 notes.
-
m9: This review discusses an array of methods to engineer more effective bNAbs for immunotherapy. Antibody m9 is an example of engineering through directed evolution; its breadth was increased through sequential affinity panning.
Hua2016
(immunotherapy, review)
-
M9: The complexity of the epitopes recognized by ADCC responses in HIV-1 infected individuals and candidate vaccine recipients is discussed in this review. M9 is discussed as CD4i-targeting, anti-gp120 Cluster B mAb which mediates ADCC.
Pollara2013
(effector function, review)
-
m9: ADCC mediated by CD4i mAbs (or anti-CD4i-epitope mAbs) was studied using a panel of 41 novel mAbs. Three epitope clusters were classified, depending on cross-blocking in ELISA by different mAbs: Cluster A - in the gp120 face, cross-blocking by mAbs A32 and/or C11; Cluster B - in the region proximal to CoRBS (co-receptor binding site) involving V1V2 domain, cross-blocking by E51-M9; Cluster C - CoRBS, cross-blocking by 17b and/or 19e. The ADCC half-maximal effective concentrations of the Cluster A and B mAbs were generally 0.5-1 log lower than those of the Cluster C mAbs, and none of the Cluster A or B mAbs could neutralize HIV-1. Cluster A's A32- and C11-blockable mAbs were suggested to recognize conformational epitopes within the inner domain of gp120 that involve the C1 region. Neutralization potency and breadth were also assessed for these mAbs. No correlation was found between ADCC and neutralization Abs' action or functional responses.
Guan2013
(antibody interactions, effector function)
-
m9: Crystal structures of gp120 and gp41 in complex with CD4 and/or MAbs 17b, 48d, b12, b13, 412d, X5, 211C, C11, 15e, m6, m9 and F105 were used to determine the structure and the mobility of the gp41-interactive region of gp120. Elements determined to maintain the gp120-gp41 interaction were the gp120 termini and a newly described invariant 7-stranded β-sandwich. Structurally plastic elements of gp120 responsible for the various gp120 conformation changes due to receptor- or Ab-binding were structured into 3 layers, with the V1/V2 loops emanating from layer 2 and the highly glycosylated outer domain from layer 3.
Pancera2010a
(antibody binding site, structure)
-
m9: MAb m9 showed superior neutralization potency compared to b12, 2F5, 4E10, scFv 17b and 2G12 in several cell-line based assays neutralizing viruses of subtypes A, B, C, D, AE and AG. In addition, m9 showed higher neutralization potency in the M7-Luc assay than in the TZM-based assay due to the lower coreceptor density in the M7-Luc cells. This Ab also potently inhibited cell-to-cell transmission of HIV-1 and lacked autoreactivity with autoantigens. Unlike X5 and 17b, m9 competed with R5Nt for binding to gp120, indicating that the epitope for m9 differs from those of 17b and X5. In vitro passaging of HIV-1 in the presence of m9 did not result in emergence of virus escape mutants to this Ab.
Zhang2010
(antibody binding site, autoantibody or autoimmunity, neutralization, variant cross-reactivity, escape)
-
m9: Fusion of CD4 with m9 scFv resulted in CD4-scFvm9 reagent with neutralization potency comparable to other CD4-CD4i complexes. The neutralization potency was improved by inclusion of an IgG Fc region and by linkage of CD4 to the heavy chain of m9. The resulting CD4hc-IgG1m9 neutralized a range of clade A, B and C viruses.
West2010
(neutralization, variant cross-reactivity, subtype comparisons)
-
m9: A review about the in vivo efficacy of MAbs against HIV-1, and about inhibition of HIV-1 infection by MAb fragments (Fab, scFv), including single molecules or fusion proteins of m9. Also, the efficacy of engineered human Ab variable domains or "domain antibodies" (dAbs) as therapeutic agents is reviewed.
Chen2009b
(neutralization, immunotherapy, review)
-
m9: This review summarizes m9 Ab epitope, properties and neutralization activity. The effect of differential CCR5 cell surface expression on m9 neutralization activity is discussed.
Kramer2007
(co-receptor, neutralization, review)
-
m9: This minireview summarizes data on differences in neutralizing activities of MAbs and pooled human sera using a traditional primary cell neutralization assay and the more standardized TZM-bl reporter cell line assay. Also, suggestions are made on how to improve and standardize neutralization assays for comparable use in different laboratories. m9 neutralization was tested against a panel of 60 HIV-1 primary isolates (10 each from clades A-D, CRF01_AE and CRF02_AG) in the two assays. 7 viruses from the PBMC assay and 13 viruses from the TZM-assay were not neutralized by this Ab. Thus, m9 showed better neutralization in the PBMC system. In total, however, the assay discordances were shown to be bi-directional and not attributable to assay sensitivity.
Polonis2008
(assay or method development, neutralization, review)
-
m9: A newly identified domain Ab m36 exhibited twofold higher neutralization potency than m9 against HIV-1 isolates from clades A, B and C. m9 neutralized a clade D HIV-1 isolate more potently than m36.
Chen2008
(neutralization, variant cross-reactivity)
-
m9: Novel approaches based on sequential (SAP) and competitive (CAP) antigen panning methodologies, and use of antigens with increased exposure of conserved epitopes, for enhanced identification of broadly cross-reactive neutralizing Abs are reviewed. Abs identified by these methods are described.
Zhang2007
(review)
-
m9: The structure of the V3 region in the context of gp120 core complexed to the CD4 receptor and to the m9 Ab was attempted to be determined by X-ray resolution, but only the structure for V3 complexed with CD4 and X5 Ab was solved.
Huang2005
(structure)
-
m9: Neutralization of HIV-1 primary isolates from different clades (A, B, C, D and E) by m9 was determined in cells expressing high or low surface concentrations of CD4 and CCR5 receptors. CD4 cell surface concentration had no effect on the inhibitory activity of this Ab while the CCR5 surface concentration had a significant effect decreasing the 50% inhibitory concentration of m9 in cell lines with low CCR5.
Choudhry2006
(co-receptor, neutralization, variant cross-reactivity, subtype comparisons)
-
m9: This antibody was selected by subjecting a random mutagenesis library of the scFv X5 to sequential rounds of selection on non-homologous HIV-1 envelope glycoproteins dubbed sequential antigen panning (SAP). scFv m9 has higher neutralization activity and is able to inhibit a broader range of HIV-1 primary isolates compared to scFv X5.
Zhang2004
(antibody generation, enhancing activity, neutralization)
References
Showing 14 of
14 references.
Isolation Paper
Zhang2004
Mei Yun Zhang, Yuuei Shu, Donna Rudolph, Ponraj Prabakaran, Aran F. Labrijn, Michael B. Zwick, Renu B. Lal, and Dimiter S. Dimitrov. Improved Breadth and Potency of an HIV-1-Neutralizing Human Single-Chain Antibody by Random Mutagenesis and Sequential Antigen Panning. J. Mol. Biol., 335(1):209-219, 2 Jan 2004. PubMed ID: 14659751.
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Chen2008
Weizao Chen, Zhongyu Zhu, Yang Feng, and Dimiter S. Dimitrov. Human Domain Antibodies to Conserved Sterically Restricted Regions on gp120 as Exceptionally Potent Cross-Reactive HIV-1 Neutralizers. Proc. Natl. Acad. Sci. U.S.A., 105(44):17121-17126, 4 Nov 2008. PubMed ID: 18957538.
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Chen2009b
Weizao Chen and Dimiter S. Dimitrov. Human Monoclonal Antibodies and Engineered Antibody Domains as HIV-1 Entry Inhibitors. Curr. Opin. HIV AIDS, 4(2):112-117, Mar 2009. PubMed ID: 19339949.
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Choudhry2006
Vidita Choudhry, Mei-Yun Zhang, Ilia Harris, Igor A. Sidorov, Bang Vu, Antony S. Dimitrov, Timothy Fouts, and Dimiter S. Dimitrov. Increased Efficacy of HIV-1 Neutralization by Antibodies at Low CCR5 Surface Concentration. Biochem. Biophys. Res. Commun., 348(3):1107-1115, 29 Sep 2006. PubMed ID: 16904645.
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Guan2013
Yongjun Guan, Marzena Pazgier, Mohammad M. Sajadi, Roberta Kamin-Lewis, Salma Al-Darmarki, Robin Flinko, Elena Lovo, Xueji Wu, James E. Robinson, Michael S. Seaman, Timothy R. Fouts, Robert C. Gallo, Anthony L. DeVico, and George K. Lewis. Diverse Specificity and Effector Function Among Human Antibodies to HIV-1 Envelope Glycoprotein Epitopes Exposed by CD4 Binding. Proc. Natl. Acad. Sci. U.S.A., 110(1):E69-E78, 2 Jan 2013. PubMed ID: 23237851.
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Hua2016
Casey K. Hua and Margaret E. Ackerman. Engineering Broadly Neutralizing Antibodies for HIV Prevention and Therapy. Adv. Drug Deliv. Rev., 103:157-173, 1 Aug 2016. PubMed ID: 26827912.
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Huang2005
Chih-chin Huang, Min Tang, Mei-Yun Zhang, Shahzad Majeed, Elizabeth Montabana, Robyn L. Stanfield, Dimiter S. Dimitrov, Bette Korber, Joseph Sodroski, Ian A. Wilson, Richard Wyatt, and Peter D. Kwong. Structure of a V3-Containing HIV-1 gp120 Core. Science, 310(5750):1025-1028, 11 Nov 2005. PubMed ID: 16284180.
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Kramer2007
Victor G. Kramer, Nagadenahalli B. Siddappa, and Ruth M. Ruprecht. Passive Immunization as Tool to Identify Protective HIV-1 Env Epitopes. Curr. HIV Res., 5(6):642-55, Nov 2007. PubMed ID: 18045119.
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Pancera2010a
Marie Pancera, Shahzad Majeed, Yih-En Andrew Ban, Lei Chen, Chih-chin Huang, Leopold Kong, Young Do Kwon, Jonathan Stuckey, Tongqing Zhou, James E. Robinson, William R. Schief, Joseph Sodroski, Richard Wyatt, and Peter D. Kwong. Structure of HIV-1 gp120 with gp41-Interactive Region Reveals Layered Envelope Architecture and Basis of Conformational Mobility. Proc. Natl. Acad. Sci. U.S.A., 107(3):1166-1171, 19 Jan 2010. PubMed ID: 20080564.
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Pollara2013
Justin Pollara, Mattia Bonsignori, M. Anthony Moody, Marzena Pazgier, Barton F. Haynes, and Guido Ferrari. Epitope Specificity of Human Immunodeficiency Virus-1 Antibody Dependent Cellular Cytotoxicity (ADCC) Responses. Curr. HIV Res., 11(5):378-387, Jul 2013. PubMed ID: 24191939.
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Polonis2008
Victoria R. Polonis, Bruce K. Brown, Andrew Rosa Borges, Susan Zolla-Pazner, Dimiter S. Dimitrov, Mei-Yun Zhang, Susan W. Barnett, Ruth M. Ruprecht, Gabriella Scarlatti, Eva-Maria Fenyö, David C. Montefiori, Francine E. McCutchan, and Nelson L. Michael. Recent Advances in the Characterization of HIV-1 Neutralization Assays for Standardized Evaluation of the Antibody Response to Infection and Vaccination. Virology, 375(2):315-320, 5 Jun 2008. PubMed ID: 18367229.
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West2010
Anthony P. West, Jr., Rachel P. Galimidi, Christopher P. Foglesong, Priyanthi N. P. Gnanapragasam, Joshua S. Klein, and Pamela J. Bjorkman. Evaluation of CD4-CD4i Antibody Architectures Yields Potent, Broadly Cross-Reactive Anti-Human Immunodeficiency Virus Reagents. J. Virol., 84(1):261-269, Jan 2010. PubMed ID: 19864392.
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Zhang2007
Mei-Yun Zhang and Dimiter S. Dimitrov. Novel Approaches for Identification of Broadly Cross-Reactive HIV-1 Neutralizing Human Monoclonal Antibodies and Improvement of Their Potency. Curr. Pharm. Des., 13(2):203-212, 2007. PubMed ID: 17269928.
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Zhang2010
Mei-Yun Zhang, Andrew Rosa Borges, Roger G. Ptak, Yanping Wang, Antony S. Dimitrov, S. Munir Alam, Lindsay Wieczorek, Peter Bouma, Timothy Fouts, Shibo Jiang, Victoria R. Polonis, Barton F. Haynes, Gerald V. Quinnan, David C. Montefiori, and Dimiter S. Dimitrov. Potent and Broad Neutralizing Activity of a Single Chain Antibody Fragment against Cell-Free and Cell-Associated HIV-1. mAbs, 2(3):266-274, May-Jun 2010. PubMed ID: 20305395.
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